Day 14: Thursday - The Road to Progression

A new pill claims to squash depression, beat chronic pain, keep your sex life roaring--and work almost instantly. Read on to find out just how happy we should be

Abject misery may sound like a cliche--until you've felt it. Back in college, I was often unable to sleep longer than 45 minutes at a stretch. I couldn't think well, and I couldn't stop thinking. Food nauseated me, and I lost so much weight I could almost watch myself disappear in the mirror. Simply put, my depression had become intolerable, and, seemingly, incurable.

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That is, until I lucked upon a medicine that, for me at least, has pretty much deserved the sobriquet "miracle drug": fluoxetine, a.k.a. Prozac. Not long after Eli Lilly's mood-boosting blockbuster hit pharmacy shelves in 1987, I was clutching a prescription and praying that Prozac would live up to all of its prerelease hype. My initial review wasn't favorable: I still felt a magnetic attraction to bridge abutments while driving. But after 5 weeks and an increase in dosage, my symptoms abated almost entirely, and I was restored to my "normal" self--neurotic, to be sure, but no longer lethally so.

I still take Prozac on a maintenance basis, to prevent relapses or reduce their severity, and because its chemical cousins--Paxil, Zoloft, Luvox, Celexa--haven't given me any meaningful reason to make a switch. Enter Cymbalta, the newest of the new antidepressants, and Eli Lilly's attempt at an encore to its greatest hit.

Widely expected to win FDA approval in late June, Cymbalta is supposed to be more effective at treating depression, anxiety, and related disorders; have a lower incidence of nasty side effects, including sexual problems; and maybe even work a little faster than the best current antidepressants, which tend to require 2 to 6 weeks minimum to kick in.

But the big news is that it could have a major impact on the treatment of depression attended by its evil twin: chronic pain.

Now that my dark moods are in check, I fantasize about freeing myself from my physical aches, as well. I'll admit I have a low pain threshold, which is probably a companion to my lifelong depression. But I've also suffered a smorgasbord of sports injuries, so something is always giving me trouble--my lower back, shoulder, hip, or some internal organ. I pop ibuprofen like Pez. So as word of Cymbalta's dual purpose filtered out, I began to wonder if I should switch from Prozac, and fix both body and soul with one swallow.

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THE BODY BLUES

Clearly, I'm not the only person who could use a one-stop remedy. In a recent study published in the Archives of General Psychiatry, researchers at Stanford school of medicine looked at data from 18,980 men and women in five European countries and found that a whopping 43 percent of those with major depression also suffered chronic pain, especially headaches and back pain. Only 17 percent of the undepressed population ached as often.

"I was surprised by how many people who were depressed also had chronic pain," says the study's lead author, Alan Schatzberg, M.D., a professor of psychiatry and behavioral sciences at Stanford. In fact, chronic pain is so common, he believes it should be added to the standard checklist of depression symptoms (changes in mood, appetite, sex drive, and sleep patterns).

Adding chronic pain to the roster could be especially valuable in diagnosing men, says David J. Goldstein, M.D., Ph.D., an associate professor of pharmacology and toxicology at the Indiana University school of medicine. "There's clearly a large proportion of male patients who downplay feeling depressed but present instead with pain that has no obvious cause, like headaches or back pain." Often, these men will also suffer classic depression symptoms like sleep disturbance or reduced sex drive but blame this entirely on their physical pain, not their mood. "This denial can be confusing to physicians," Dr. Goldstein adds, "and often leads to misdiagnosis." The unfortunate result: Such patients aren't treated for what truly ails them.

But is Cymbalta the answer? Recently, Dr. Goldstein decided to find out. In the January/February 2004 issue of Psychosomatics, he and his colleagues published an analysis of three randomized, double-blind, placebo-controlled trials. The findings: When compared with a placebo, Cymbalta significantly reduced overall pain, back pain, shoulder pain, and time in pain while awake. Perhaps not too surprisingly, for most patients, physical improvement tended to parallel mood improvement--like dancers following each other's lead.

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And while this research was funded by Eli Lilly (de rigueur for any drug in development), the science behind Cymbalta backs up the findings. Prozac and the other selective serotonin reuptake inhibitors (SSRIs) primarily target a single feel-good neurotransmitter: serotonin. Cymbalta affects both serotonin and norepinephrine, a neurotransmitter that helps to regulate alertness, energy, excitement, and concentration. In fact, the dual action of this so-called SNRI has more in common with the old tricyclic antidepressants, some of which, like Elavil, are still used to treat depression and chronic pain.

The reason doctors moved on from the tricyclics--which were helpful with mood--was their wide array of potential side effects, including urine retention, constipation, arrhythmic heartbeat, blurry vision, and a host of other unsavory problems. Cymbalta may function as a "clean" tricyclic--all the benefits, fewer side effects. Or at least, that's the hope.

"Generally, you do pay a price for taking a medication with a second mechanism of action," says Michael E. Thase, M.D., a depression expert at the University of Pittsburgh medical center. "You may see, for example, a little more dizziness, insomnia, sweating, or rapid pulse. None of these are likely to be nearly as bad as with the tricyclics. But there is no free lunch here."

SURVIVING THE SPIN FACTORY

Since Prozac first landed in pharmacies nearly 17 years ago, the market for antidepressants has ballooned to nearly $14 billion in the United States, says stock analyst Scott Shevick, who follows the major-pharmaceuticals sector for the investment firm Bear, Stearns & Co. Last year, more than 213 million prescriptions for antidepressants were dispensed, mostly SSRIs in one form or another. Without a doubt, a new antidepressant could prove to be a windfall for its manufacturer.

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"Forecasting individual drugs is incredibly hard to do," Shevick says. "But Lilly knows the psychopharmacology market better than anybody, and they'll be throwing 5,300 reps at physicians to sell the hell out of this drug."

Indeed, in coming months, Shevick says Lilly is likely to barrage doctors and would-be patients alike, pushing Cymbalta's supposed advantages over the competition. We're likely to be barraged, too, by cautionary words and horror stories from antidepressant critics, ranging from reputable researchers to "fringe groups" like the Church of Scientology, which, Shevick says, has been lobbying to have Prozac banned since it first came on the market.

Sorting through all the hype and nuttiness won't be easy, but here are a few of the questions likely to be raised.

Will Cymbalta have the same sexual side effects as the SSRIs? "When the SSRIs first hit the market," says Joseph Glenmullen, M.D., a Harvard psychiatrist and the author of Prozac Backlash, "it was thought that incidence of sexual side effects was only 5 percent.

We now know that 60 percent of patients have some sexual problems." The rates of sexual dysfunction with Cymbalta, by comparison, have been extensively studied using rating scales, says David Dunner, M.D., director of the center for anxiety and depression at the University of Washington at Seattle. "It appears that only about 10 percent to 15 percent of men will have some kind of sexual dysfunction," he says.

Dysfunction is defined as anything from reduced sexual desire and/or trouble getting an erection to delayed orgasm, or even anorgasmia--the technical term for life without whoopee. For those men who develop erectile difficulties, Dr. Dunner adds, Viagra and its brothers can usually help. The only cure for anorgasmia, however, is lowering the antidepressant dosage or avoiding the drug entirely.

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How does Cymbalta compare with Effexor? Though Cymbalta has been shown to be 5 to 10 percent more likely than SSRIs to provide complete relief from depression, the same can also be said about Effexor (venlafaxine), the other SNRI available in the United States. Effexor, however, appears to affect norepinephrine only at high dosages, which, in 10 percent to 12 percent of patients, also cause dangerously elevated blood pressure. The data from Cymbalta's clinical trials are much more reassuring: Only 1.3 percent of patients experienced increases in blood pressure. Still, such a selling point may prove short-lived. "Since Effexor XR, the extended-release form, hit the market," says Shevick, "you rarely hear about high blood pressure being a problem."

Will Cymbalta act more quickly than other antidepressants? Generally speaking, people have to take the currently available antidepressants for 2 to 6 weeks before they notice improvement. Eli Lilly claims that Cymbalta may act faster. Michael Detke, M.D., Ph.D., associate medical director for Lilly, argues that the drug's dual action allows it to simultaneously hit depression, anxiety, reduced concentration, low energy, and physical pain. Because it attacks on several fronts, he says, the patient may notice improvement faster. Anecdotally, at least, some patients corroborate this. "There's a possibility this could be true," says Dr. Thase. "But at this point, the studies that are needed to prove it have not been done."

Didn't a patient commit suicide during the testing of Cymbalta? Early last February, a 19-year-old college student serving as a "normal control" in a Cymbalta trial hung herself from a shower rod at a Lilly research lab. Investigators determined that the young woman was actually on a placebo at the time of her death, though she had earlier been receiving relatively large doses of the active medication. Lilly claims its drug played no role in the woman's death, a conclusion with which many outside observers agree. "The FDA is very risk averse," says Dr. Goldstein. "If they believed that Cymbalta caused suicide, they would stop further development."

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A CLOSE CALL

If Cymbalta gets a thumbs-up from the FDA, guys like me will be faced with a decision:

Stay the course with medication that's already working pretty well--or embrace the promise of a potentially better remedy?

When I ask for advice from Dr. Dunner, he tells me, "One of the first things I learned in psychiatry was not to rock the boat. Depression is a complex illness, and the reasons for switching from an effective medication ought to be compelling--a less-than-full response, for example, or a deeply troubling side effect."

But Prozac works for me, and I can tolerate the side effects. In fact, the only "problem" I've endured is slightly delayed ejaculation--a problem my wife doesn't seem to mind at all.

Cost also figures strongly on the "stay the course" side of the equation. As a self-insured man, I pay for most prescriptions out of pocket. Now that Prozac is available as generic fluoxetine, it's become nearly as cheap as aspirin--and I'm in no rush to go back to pills that Shevick forecasts could cost well over $3 a pop.

"Effective" and "cheap" are two adjectives that are hard to ignore. Regardless of Cymbalta's fate, I've decided to stay with the miracle drug that's helped me so much so far. For guys who've been let down by SSRIs, or for those newly diagnosed with depression, Cymbalta could prove to be a better option.

Who knows? I may even join them one day.

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"Some patients have reported that over time, a given antidepressant doesn't work quite as well anymore," says Dr. Goldstein. Practitioners refer to this as "Prozac poop-out"--though anecdotal cases have been reported with all the antidepressants, not just fluoxetine. In such cases, says Dr. Goldstein, "it might be the time to try a dual-activity antidepressant like Cymbalta."

And that's why I follow all the advances in antidepressants. As another barrier between me and abject misery, Cymbalta is already a miracle drug--even if I never end up needing to take it.

Stress: Cereal Stress-Killer

A bowl beats tension

Research has discovered another good reason to eat cereal at breakfast (besides the riveting prose on the box). A recent study from Wales shows that regular consumption of breakfast cereal is associated with reduced stress and improved physical and mental health. Those who ate cereal daily had lower levels of cortisol, a hormone that rises with stress. Further research to explain the link is under way. With any luck, fun marshmallow shapes will only increase the benefits.

Guy Wisdom: Road Warriors

By now, you've learned to deal with horrible drivers, especially if you've been to Boston. But sometimes it's you, not other people, causing the trouble. Here's how to deal with unexpected crises.

THE MESS: Traffic is slow and your car's overheating.THE FIX: Stay at least one car length behind the vehicle in front of you, turn on the heater, and drive at a steady pace. With more following distance, your radiator will suck in less hot exhaust from other cars, and the heater will draw heat away from the engine. If you see steam, pull over or risk expensive engine damage, advises John Paul, car doctor for AAA of Southern New England.

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THE MESS: You blew through the automatic toll lane, and your payment didn't register.

THE FIX: Keep going. Odds are you won't be penalized for missing one payment. But more than one flyby will usually cost you at least $50, says MassPike spokesman Doug Hanchett.

THE MESS: Your car dies in the left lane.THE FIX: Turn on your hazard lights. Wait inside the car for your tow, and get out only if it's safe--meaning traffic is at a crawl. "Stay in front of the vehicle so there's always something between you and oncoming traffic," Hanchett says.

THE MESS: Your gas pedal sticks.THE FIX: Shift to neutral and brake as you normally would. "It'll make a lot of noise, but you won't be going anywhere," says Bill Buff, a driving instructor in New Jersey. If necessary, turn the ignition off one click. This disables the power steering and slows acceleration, but braking and steering will be difficult.

THE MESS: Your brakes fail.THE FIX: Downshift to slow the engine. You can also pump the emergency brake while holding down the release button. Don't pull too hard or you'll skid. As a last resort at slow speeds, steer up against the curb to stop. "It isn't going to be pretty, but hopefully it'll get the job done," Paul says.

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